Horizontal gene transfer

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Horizontal gene transfer occurs when an organism transfers its genetic material to a being other than one of its own offspring. The actual process of this transfer can be by any mechanism, but because genes are not passing by descent, horizontal gene transfer (abbreviated as HGT) is always very different from vertical gene transfer. In vertical descent, parental traits are inherited by progeny by one of two general methods: either (1) sexual reproduction in which gametes form zygotes, a common method in higher animals and plants, or (2) by asexual reproduction: splitting of cells, as is usual in bacteria and fungi, or an entire organism growing from a fragment, as happens in some animals and plants. HGT is a much more recently discovered route of passage for genetic material; it is relatively common in microorganisms, and to a lesser extent in plants.[1] Biologists have also observed transfer of genes from bacteria to multicellular organisms.[2] By HGT, genetic material can be shared between organisms without the immediate relatedness of mother cell to daughter cells, or parent organisms to offspring; indeed, by HGT material can pass between organisms that are not even of the same species, genus, sub-kingdom or kingdom of life form. HGT (sometimes called lateral gene transfer) is very much less common than vertical gene transfer, so its detection requires special techniques.

Introduction

Evidence from genome science and bioinformatics shows that HGT has occurred between diverse biological taxa that are widely separated in the phylogenetictree of life. Known HGTs include movement of genetic material between different species of microbes and other microbial taxa such as protists, gene movement between different plant families, between different animals, and between bacteria and plants.

Microorganisms appear to be most affected by HGT, but even in microbes only about 2% of core genes are recognized as having been laterally transferred. Because this percentage is so low, the main lineages of microbial evolution can still be treated as 'trees' branched by vertical descent, with HGT included in the scheme only as 'cobwebs' (see figure at right).

Gene transfers between different biological sub-kingdoms (domains), such as between eukaryotic protists and bacteria, or between bacteria and insects are the most phylogenetically extreme cases of HGT. An example is bacterial 'rol' genes from Agrobacterium species which have been found in tobacco plants (Nicotiniana). Wolbachia are symbiotic bacteria that reside within tissues many insects, and transfer of genes from such parasitic or endosymbiotic bacteria into the chromosomes of their host is well established. In fact, in the fruit-fly Drosophila ananassae a complete genome of a Wobachia parasite has been detected, inserted within the an insect chromosome. Several other fragments of Wolbachia genomes have been detected in various insect genomes.[3]

HGT is just one of several processes that can cause rearrangement of genomes during evolution. The possibility of intracellular movement of genes between different parts of an organism's genome (that is, between the chromosomes of the nucleus, the circular mitochondrion chromosome, or the circular plastid (chloroplast) chromosome) needs to be considered when evaluating HGT between different species.[4]

Main features of HGT in nature

A hallmark of HGT is the presence of the same gene in organisms that are only very distantly related to each other. The frequent discovery of shared DNA sequences such as the mariner class of transposons, insertion sequence DNA, retrovirus genes in diverse species and shared mitochondrial genes in diverse flowering plants indicate that mobile DNA has natural pathways for movement between species. (The name mariner for a class of related transposons is an allusion to The Rime of the Ancient Mariner, meaning a traveller to distant lands.) Close relatives of mariner mobile DNA have been identified in organisms as diverse as mites, flatworms, hydras, insects, nematodes, mammals and humans.[5]

Millet. From: Jumping Genes Cross Plant Species Boundaries.Analysis of the genomes of millet and rice revealed evidence for HGT between chromosomes in the nucleus of one plant to chromosomes in the nucleus of a reproductively isolated species

Horizontal movement of genes is common among bacteria, and is a major factor in accelerating the rate of their evolution. HGT is involved in multiple-antibiotic resistance in pathogenic bacteria, and this is a major factor that is limiting the effectiveness of antibiotics. Inter-domain (sub-kingdom) transfer of several genes from eukaryotes to bacteria for instance, has occurred in the 'accidentally pathogenic' bacterium (Legionella pneumophila, see illustration) that lives within vacuoles of protist and mammalian macrophage cells.[6]

HGT is documented in diverse unicellular protists, which can contain several genes transferred from both prokaryotes and other protists.[7]

HGT occurs globally on a massive scale among marine microorganisms. Viruses, which, at total numbers near 1029 are the most common biological entities in the sea, are a major pathway for gene movement between different species. It has been estimated that, on average, 1013 virus-mediated gene transfer events occur in the Mediterranean sea each year. Endosymbiosis with an alga is identified as a route for HGT in marine dinoflagellates, the organisms that cause 'red tides'.[8]

Interspecies gene movement by cross-hybridization is common in flowering plants. Mechanisms for HGT in flowering plants between more distant taxa involving parasitic plants such as dodder and endophytes (such as mosses, which are in intimate cell-to-cell contact with their host plants) are also well established (see Horizontal gene transfer in plants). Plant mitochondria can be unusually active in HGT.

Not all of the ways in which HGT occurs are fully characterized, but some have been identified. HGT is hard to detect directly, as it is relatively rare within a species, but can be detected by modern DNA analysis which can enable detailed comparison of genomes. In insects, mites and viruses are probably vectors for HGT. In certain bacteria, surface appendages called pili have various roles in DNA uptake, DNA secretion and DNA transfer which have been extensively analyzed; HGT in bacteria includes plasmid-mediated promiscuous mating by bacteria (for instance by the crown-gall bacterium Agrobacterium tumefaciens) and carriage of genes between species by viruses. Direct DNA uptake is another transfer mechanism, as illustrated by Legionella bacteria, which are naturally competent for DNA uptake.

Eukaryotes

Protists

Analysis of the complete genome sequence of the protist Entamoeba histolytica indicates 96 cases of relatively recent HGT from prokaryotes. There is also convincing evidence that a bacterial gene for a biosynthetic enzyme has been recruited by the protist Trichomonas vaginalis from bacteria related to the ancestors of Pasteurella bacteria. Similar analysis of the protist Cryptosporidium parvum reveals 24 candidates of HGT from bacteria. These results fit the idea that 'you are what you eat'. That is, in unicellular grazing organisms, foreign genetic material is constantly entering the cell from food organisms, and occasionally some of this material enters the genome.[9]

Fungi

Comparison of the genome sequences of two fungi, baker's yeast (Saccharomyces cerevisiae) and Ashbya gossypii, has shown that Saccharomyces has received two genes from bacteria by HGT. One of these genes codes for an enzyme that allows baker's yeast to make pyrimidine nucleotide bases anaerobically, and the other allows usage of sulfur from several organic sulfur sources. Other work with yeasts suggests that eight genes from Yarrowia lipolytica, five from Kluyveromyces lactis, and one from Debaryomyces hansenii are horizontally transferred.[10].Other movement of bacterial genes to fungi has been well documented from studies of rumen and soil fungi.[11]

Other eukaryotes

Analysis of DNA sequences suggests that HGT has also occurred within multicellular eukaryotes, by a route that involves transfer of genes from chloroplast and mitochondrial genomes to the nuclear genomes.[12] According to the endosymbiotic theory, chloroplasts and mitochondria originated as the bacterial endosymbionts of a progenitor to the eukaryotic cell, and endosymbiosis can be considered to be a special case of HGT.

It has also been discovered that plant genes can move to endophyte fungi that grow on them. Several plant endophyte fungi that grow on taxol-producing yew trees have gained the ability to make taxol themselves.[13] (Taxol, also called paclitaxel, is an anti-cancer drug found in yew trees.)

Animals and insects

Junk DNA is the most obvious general evidence of HGT in eukaryotes. Junk DNA is the name given to the seemingly non-functional repetitive DNA sequences that are a major portion of the genomes of many plants and animals. This DNA usually includes multiple copies of various 'Jumping genes' which can proliferate within a genome after they have been transferred from another species. Examples in the human of such mobile elements are 'Hsmar1' and 'Hsmar2' which are related to the widely studied 'mariner' transposon. Close relatives of mariner mobile DNA have been discovered in organisms as diverse as mites, flatworms, hydras, insects, nematodes, mammals and humans.[14]Retroviruses and retrotransposons are other examples of mobile horizontally transferred DNA found in animals.

It has been postulated that movement of genes from bacteria was a key event in nematode worm evolution. At least 12 genes have been identified in the nematode plant parasite Meloidogyne as likely to have originated from bacteria, including genes for plant cell wall degradation.[15]

The adzuki bean beetle Callosobruchus chinensis is infected with several strains of bacterial Wolbachiaendosymbionts, and provides yet another example of horizontal gene transfer. A genome fragment of one of these endosymbionts has been found transferred to the X chromosome of the host insect.[16]

Decoding the tree of life from genomes scrambled by HGT

Because each organism carries a record of its ancestry in its DNA, methods for rapid gene isolation and analysis of DNA encoded sequences - which can extract the information from this ancestral archive - have been important for answering questions about evolution, and they have enabled rapid expansion of the field of biological systematics known as phylogenetic inference. Comparison of related (homologous) gene sequences from different organisms has made it possible to reconstruct the history of many evolutionary lineages.[17]
Many issues about evolution have been clarifed by comparing homologous genes from different species, genera, families, and phyla. Unfortunately, HGT complicates the picture, because HGT 'scrambles' the evidence needed to deduce the branching patterns of evolutionary trees. One area of current research in phylogenetic inference, and arguably one of the most challenging problems in evolutionary theory, is the early stages in the evolution of life. This quandary about the origins of different cell types provides a good illustration of the complications introduced by HGT into the reconstruction of evolutionary history.

The main early branches of the tree of life have been intensively studied by microbiologists because the first organisms were microrganisms. A gene very often used for constructing phylogenetic relationships in microorganisms is the small ribosomal subunit ribosomal RNA (SSU rRNA) gene, as its sequences tend to be conserved among members with close phylogenetic distances, yet it is variable enough that differences can be measured.[18] The use of SSU rRNA to measure evolutionary "distances" was pioneered by Carl Woese when formulating the first modern 'tree of life', and his results led him to propose the Archaea (single celled organisms superficially similar to bacteria) as a third domain (sub-kingdom) of life.

A three domain representation of the tree of life based on SSU rRNA sequences, showing the separation of Bacteria, Archaea, and Eukaryote domains. See Microorganisms article for further explanation

Microbiologists introduced the term domain for the three main early branches of the tree of life, where domain is a phylogenetic term very similar in meaning to biological kingdom. These represent the three main lineages in evolution of early cellular life, and are currently represented by the Bacteria, the Archaea and Eukarya (eukaryote) domains. Eukaryotes are all organisms with a well defined nucleus, and this domain comprises protists, fungi, and all organisms in the animal and plant kingdoms, including humans. As seen in the figure (left), studies of SSU rRNA genes (and some other genes) might suggest that Archaea and Eukarya have a sister relationship in evolution, and it has often been assumed that eukaryotes evolved from archaeal cells. However, the fact that genes can move between distant branches of the tree of life even at low probabilities poses problems for scientists trying to reconstruct evolution from studying genes and gene sequences in different organisms due to the scrambling effect of HGT. The challenges are most awkward for the ambitious reconstruction of the earliest branches of the tree of life - because over a long enough time and with large numbers of organisms, many HGT events are certain to have occurred even though each particular transfer event has a low probability.

Thus recent discoveries of 'rampant' HGT in microorganisms, and the detection of horizontal movement of genes for SSU rRNA have forced biologists to question the accuracy of at least the early branches in the tree of life, and even to question the validity of trees as useful models of microbial evolution.[19]

Recent efforts to infer evolutionary trees while recognizing HGT

The challenges of ascertaining an accurate branching structure for evolutionary trees of microbes, especially the earliest branches in the tree of life, have been a great spur for current biological research. Clear answers to important questions about these trees are not yet available, but many interesting discoveries and ideas are emerging.

Instead of relying primarily on a single gene such as the SSU rRNA gene to reconstruct evolution, scientific effort has now shifted to exploiting the comprehensive information from the many complete genome sequences of organisms that are now available.[20] So far, this comparative genomics approach, made possible by specially developed computer programs and mathematical algorithms, suggests that most of the core genes of bacteria that are useful for deducing evolutionary histories are unaffected by HGT. This confirms the practical experience of microbiologists that consistent and reliable trees can still be deduced for the more recent stages in microbial evolution, such as evolutionary relationships within particular bacterial phyla. This does require, however, using multiple, well chosen genes to investigate how lineages are related to one another. Thus the 'tree' is still a valid metaphor for microbial evolution - but a tree adorned with 'cobwebs' of horizontally transferred genes.

But it is also clear that trees based only on SSU rRNA alone do not capture the events of early eukaryote evolution accurately, and the origins of the first nucleated cells are still uncertain. For instance, careful analysis of the complete genome of the eukaryote yeast shows that many of its genes are more closely related to bacterial genes than they are to archaea, and it is now clear that archaea were not the simple progenitors of the eukaryotes. This discovery is a stark contradiction to earlier findings based on SSU rRNA and limited samples of other genes.[21] (See Evolution of cells for further discussion.)

On the other hand, the concept that rampant HGT took place in 'gene-swapping collectives' involved in metabolism and replication at the earliest stages of life's origins, before a postulated transition to Darwinian evolution of the cellular lineages known today, has been used by Carl Woese and colleagues to develop fresh insight into the origins of the universal genetic code.[22]

Although common among bacteria, lateral gene transfer-the movement of genes between distantly related organisms-is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes.

We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire Wolbachia genome (>1 megabase) to short (<500 base pairs) insertions. Potential Wolbachia-to-host transfers were also detected computationally in three additional sequenced insect genomes.

We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts.

Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.

Where Do All Those Genes Come From? This study resolves a long-standing paradox: how is it possible to deduce reliable evolutionary histories from gene sequences in bacteria despite extensive HGT? (Open access)

Zhu J et al. (2000) The bases of crown gall tumorigenesis.J Bacteriol 182:3885-95PMID 10869063 This article describes the biology of crown-gall bacterium, and the mechanism of DNA injection by this bacterium, and explains how genes can move between bacterial species and from bacteria to eukaryotic organisms, and illustrates the extent to which different species can co-evolve. (Open access)

Acquiring genomes: a theory of the origin of species. Margulis L and Sagan D (2002) Basic Books ISBN 0-465-04392-5. A book that looks at gene transfer from a different perspective to many conventional interpretations, but with an emphasis on microbial diversity. Reviewed here.

Weinbauer MG, Rassoulzadegan F (2004) Are viruses driving microbial diversification and diversity? Envir Microbiol 6:1-11 PMID 14686936 Discussion of both the evolutionary and ecological activities of viruses in the ocean, a major source of HGT in nature.

Biology's next revolution Free access Essay, Nigel Goldenfeld and Carl Woese, Nature 445: 369 (25 January 2007) doi:10.1038/445369a; Published online 24 January 2007. The emerging picture of microbes as gene-swapping collectives demands a revision of such concepts as organism, species and evolution itself.